title: Specific de-SUMOylation triggered by acquisition of spatial learning is related to epigenetic changes in the rat hippocampus.
abstract: Histone acetyltransferase activity by transcriptional cofactors such as CREB-binding protein (CBP) and post-translational modifications by small ubiquitin-like modifier-1 (SUMO-1) have shown to be relevant for synaptic and neuronal activity. Here, we investigate whether SUMOylation of CBP plays a role in spatial learning. We assessed protein levels of CBP/p300, SUMO-1, and CBP SUMOylation in the hippocampi of rats trained on the Morris water maze task. Furthermore, we evaluated the post-translational modifications at Zif268, BDNF, and Arc/Arg3.1 promoters using chromatin immunoprecipitation with anti-Acetyl-Histone H3-Lys14 (H3K14Ac) and SUMO-1. We found that CBP/p300 protein expression is unchanged in animals trained for 7 days. However, H3K14Ac-specific histone acetyltransferase activity showed specific hyperacetylation at promoters of Zif268 and BDNF-pI but not of Arc/Arg3.1 and BDNF-pIV. In naive animals, CBP is selectively SUMOylated and the Arc/Arg3.1 promoter is differentially occupied by SUMO-1, although SUMO-1 levels are unchanged. These results suggest a specific negative regulation by SUMO-1 on CBP function and its effect on epigenetic changes triggered by spatial learning and memory processes.
authors.affiliation: aGroup of Biophysics, Institute of Physics, Faculty of Exact and Natural Sciences bCellular and Molecular Neurobiology Area, Neurosciences Group of Antioquia, School of Medicine cGENMOL, Molecular Genetics Group, School of Medicine, University of Antioquia, Medellín, Colombia dInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sergio
authors.initials: S
authors.lastname: Castro-Gomez
authors.forename: Alvaro
authors.initials: A
authors.lastname: Barrera-Ocampo
authors.forename: Gloria
authors.initials: G
authors.lastname: Machado-Rodriguez
authors.forename: John F
authors.initials: JF
authors.lastname: Castro-Alvarez
authors.forename: Markus
authors.initials: M
authors.lastname: Glatzel
authors.forename: Marco
authors.initials: M
authors.lastname: Giraldo
authors.forename: Diego
authors.initials: D
authors.lastname: Sepulveda-Falla
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006624:Hippocampus / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D025842:SUMO-1 Protein / Q000378:metabolism*; D058207:Sumoylation / Q000235:genetics*
chemical_list: D025842:SUMO-1 Protein; D050882:CREB-Binding Protein; D051548:Histone Acetyltransferases